The decapping activator Edc3 and the Q/N-rich domain of Lsm4 function together to enhance mRNA stability and alter mRNA decay pathway dependence in Saccharomyces cerevisiae

Abstract

The rate and regulation of mRNA decay are major elements in th proper control of gene expression. Edc3 and Lsm4 are two decappin activator proteins that have previously been shown to function in th assembly of RNA granules termed P bodies. Here, we show tha deletion of edc3, when combined with a removal of the glutamine asparagine rich region of Lsm4 (edc3 lsm4C) reduces mRN stability and alters pathways of mRNA degradation. Multiple teste mRNAs exhibited reduced stability in the edc3 lsm4C mutant. Th destabilization was linked to an increased dependence on Ccr4 mediated deadenylation and mRNA decapping. Unlike characterize mutations in decapping factors that either are neutral or are able t stabilize mRNA, the combined edc3 lsm4C mutant reduced mRN stability.We characterized the growth and activity of the major mRN decay systems and translation in double mutant and wild-Type yeast In the edc3 lsm4C mutant, we observed alterations in the levels o specific mRNA decay factors as well as nuclear accumulation of th catalytic subunit of the decapping enzyme Dcp2. Hence, we sugges that the effects on mRNA stability in the edc3 lsm4C mutant ma originate from mRNA decay protein abundance or changes i mRNPs, or alternatively may imply a role for P bodies in mRNA stabilization.